The present invention relates generally to nuclear magnetic resonance imaging, and more particularly to the use of hyperpolarized xenon-129 in magnetic resonance imaging and spectroscopy.
Over the past twenty years, nuclear magnetic resonance imaging (MRI) has developed into an important modality for both clinical and basic-science imaging applications. Nonetheless, advancements continue at a rapid pace. A recent notable advance was the introduction of xe2x80x9chyperpolarizedxe2x80x9d noble gases as a new contrast agent for nuclear magnetic resonance (NMR), as described, for example, in Albert MS, Cates GD, Driehuys B, et al., Biological magnetic resonance imaging using laser-polarized 129Xe, Nature 1994, 370:199-201. Prior to the introduction of hyperpolarized noble gases, under typical experimental conditions the nuclear polarization for MRI (to which the signal level, or in more general terms, the image quality, is proportional) was at most on the order of 10xe2x88x924, whereas polarizations approaching 100% are possible with hyperpolarized gases. Therefore, considering that many NMR applications are inherently limited by the available signal level, hyperpolarized gases present the possibility for a significant improvement of the affected applications, as well as the possibility for applications that were heretofore not feasible.
Of particular interest for hyperpolarized-gas NMR studies are the two nonradioactive noble-gas isotopes with a nuclear spin of xc2xd, helium-3 and xenon-129. Both nuclei are useful for imaging of gas-filled spaces, such as cracks and voids in materials (see, e.g., Song Y Q, Gaede H C, Pietrass T, et al. Spin-polarized 129Xe gas imaging of materials. J Magn Reson 1995, A115:127-130), or the lungs and sinuses in humans and animals (see, e.g., Albert M S, Cates G D, Driehuys B, et al. Biological magnetic resonance imaging using laser-polarized 129Xe. Nature 1994, 370:199-201). Xenon-129 is soluble in a variety of substances, while helium-3 in general has a very low solubility (see, e.g., Abraham M H, Kamlet M J, Taft R W, Doherty R M, Weathersby P K. Solubility properties in polymers and biological media. 2. The correlation and prediction of the solubilities of nonelectrolytes in biological tissues and fluids, J Med Chemistry 1985, 28:865-870). In particular, xenon is lipophilic, having a high solubility in oils and lipid-containing tissues. Another important characteristic of xenon-129 is an exquisite sensitivity to its environment which results in an enormous range of chemical shifts upon solution (e.g., a range of approximately 200 ppm in common solvents) or adsorption (see, e.g., Miller K W, Reo N V, Uiterkamp A J M S, Stengle D P, Stengle T R, Williamson K L. Xenon NMR: chemical shifts of a general anesthetic in common solvents, proteins, and membranes, Proc Natl Acad Sci USA 1981, 78:4946-4949). These solubility and chemical shift characteristics make xenon-129 a valuable probe for a variety of material science and biological applications.
In the medical field, dissolved-phase NMR of hyperpolarized xenon may allow perfusion imaging of the brain, lung, and other organs (such as kidneys), and offers the potential for the non-invasive characterization of other important physiological parameters. Upon inhalation, xenon dissolves rapidly into the bloodstream and is transported throughout the body, with preferential distribution to lipid-rich regions. Nonetheless, despite some remarkable results from Swanson et al. (see Swanson S D, Rosen M S, Agranoff B W, Coulter K P, Welsh R C, Chupp T E. Brain MRI with laser-polarized 129Xe, Magn Reson Med 1997,38:695-698; see also Swanson S D, Rosen M S, Coulter K P, Welsh R C, Chupp T E. Distribution and dynamics of laser-polarized 129Xe magnetization in vivo. Magn Reson Med 1999, 42:1137-1145) that demonstrated dissolved-phase xenon images from the brain, lung and heart of a rat using chemical-shift imaging, high-resolution dissolved-phase imaging in humans has remained elusive. The only in-vivo dissolved-phase images that have been obtained so far required the animals to be ventilated with xenon for extended periods of time, a technique that would appear to be impractical for use in humans.
The reasons that dissolved-phase imaging of xenon in humans has not been more successful are numerous, not the least of which is the fact that only a relatively small fraction of the inhaled hyperpolarized xenon-129 is dissolved at any point in time, and therefore the magnetization available for dissolved-phase imaging is much less than that available for gas-phase imaging. Nonetheless, if high-resolution MRI of dissolved-phase xenon were to be possible, it seems likely that a new field would emerge, yielding information of physiological and medical relevance that currently cannot be obtained using existing MRI techniques or any other available in-vivo imaging modality.
This present invention consists of the methodology and apparatus for using the signal from hyperpolarized xenon-129 nuclei in one compartment, which resonate at a given frequency determined by their chemical shift and the strength of the applied magnetic field of the NMR or MRI system, to indirectly measure, using MR spectroscopy or imaging methods, characteristics, such as the concentration, of xenon-129 nuclei in one or more other compartments which resonate at a frequency or frequencies distinct from that of the first compartment and which exchange in some manner with the nuclei of the first compartment.
For example, the first compartment could be gas-phase hyperpolarized xenon in the lung air spaces and the other compartments could be dissolved-phase hyperpolarized xenon in the lung parenchyma and in the blood of the alveolar capillary bed. For this example, our invention provides the means, among other possibilities, to acquire high-resolution magnetic resonance images of the gas-phase xenon that reflect the concentration of the dissolved-phase xenon. With an appropriate choice of parameter values, the gas-phase images subsequently created indicate the volume of lung parenchyma, an important physiological parameter of medical relevance. In this example, using variations of the method, it may be possible to measure other meaningful physiological parameters such as the lung blood volume or the lung surface to volume ratio. In essence, the invention permits the strong xenon gas-phase signal to be used as an amplifier to measure, with high resolution, characteristics of the much weaker xenon dissolved-phase signal by taking advantage of the exchange that occurs between the gas and dissolved phases. This invention thus provides the means to measure, in a non-invasive and practical fashion, various properties of the lung that cannot be measured non-invasively at a competitive resolution by any other method.
Besides the lung, the invention also has obvious application to the study and characterization of certain materials wherein hyperpolarized xenon introduced into or surrounding the material exists in distinct, chemically-shifted environments that are in exchange.